Initial Results of Phase II Study with HCV Protease Inhibitor Boceprevir in Treatment-Naive Hepatitis C Patients Show a High Rate of Early Virologic Response

... Top Line Results of Phase II Study in Previous Nonresponders also Rep...KENILWORTH N.J. Oct. 18 /- Schering-PloughCo... These initial results while preliminary are very encouraging ands...Boceprevir is being evaluated in combination with PEGINTRON and REBETO...

"These initial results, while preliminary, are very encouraging, and
showed that boceprevir is a potent antiviral agent for hepatitis C," said
Paul Kwo, M.D., associate professor of medicine and medical director, liver
transplantation, Department of Medicine, Division of
Gastroenterology/Hepatology, Indiana University School of Medicine,
Indianapolis, and the lead investigator of the study. "In this study,
boceprevir improved viral clearance rates at week 12 in genotype 1
hepatitis C infection compared to the control group. We look forward to
further results from this ongoing study."

Boceprevir is being evaluated in combination with PEGINTRON and REBETOL
for the treatment of patients chronically infected with hepatitis C virus
(HCV) genotype 1 in two large Phase II clinical studies, in which more than
800 patients have received boceprevir. One study involves treatment-naive
patients and the other involves patients who were nonresponders to previous
peginterferon and ribavirin combination therapy. In these boceprevir
studies, the most common adverse events have been fatigue, headache, nausea
and anemia. No increase in skin adverse events (rash) beyond what was seen
in the PEGINTRON and REBETOL control was observed. Gastrointestinal events
were the most common adverse events leading to discontinuation in the
boceprevir arms.

In the treatment-naive study, known as HCV SPRINT-1 (HCV Serine
Protease Inhibitor Therapy-1), boceprevir (800 mg TID) is being evaluated
in three treatment regimens: in combination with PEGINTRON (1.5 mcg/kg once
weekly) and REBETOL (800-1400 mg daily) for 28 or 48 weeks; 4 weeks of
PEGINTRON and REBETOL combination therapy at the doses described above
followed by adding boceprevir to the combination for 24 or 44 weeks; and
boceprevir in combination with PEGINTRON and low-dose REBETOL (400-1000 mg
daily) for 48 weeks, compared to a control of PEGINTRON and REBETOL alone
for 48 weeks (a standard of care). The primary endpoint of this study is
sustained virologic response. Patients receiving these boceprevir regimens
achieved a high rate of early virologic response, with 70, 79 and 54
percent of patients, respectively, having undetectable virus (HCV-RNA) at
week 12 of boceprevir therapy compared to 34 percent of patients in the
control arm (Roche Cobas Taqman 1.0 assay; lower limit of detection is 15
IU/mL). Treatment discontinuations due to adverse events were 12, 9, and 8
percent for patients in the boceprevir regimens, respectively, compared to
5 percent for the control arm.

A total of 595 patients have been treated in the HCV SPRINT-1 study at
sites across the United States, Canada and Europe, including 491 patients
treated with boceprevir. Overall, 77 percent of patients in the study were
enrolled in the United States. African-Americans represent 16 percent of
the patients enrolled in the study and 7 percent of patients in the study
are cirrhotic.

Boceprevir in "Null" Nonresponder HCV Patients

Schering-Plough also reported top line results from a completed Phase
II study evaluating boceprevir dose response and the need for ribavirin in
patients chronically infected with HCV genotype 1 who were nonresponders to
previous peginterferon and ribavirin combination therapy (i.e., patients
who did not have undetectable HCV-RNA or who did not achieve a 2 log
decline in viral load with a minimum of 12 weeks of peginterferon and
ribavirin combination therapy). These "null" nonresponders to peginterferon
and ribavirin combination therapy represent the most difficult-to-treat
patient population. Patients who relapsed following previous HCV therapy
(relapsers) were not included in this study.

This study was complex, involving seven different treatment arms.
Patients were initially randomized to low doses of boceprevir (100, 200,
400 mg TID) before initiating an 800 mg TID boceprevir arm. Under the study
protocol, patients received these boceprevir doses in combination with
PEGINTRON (1.5 mcg/kg weekly) with or without REBETOL (800-1400 mg daily)
for 24 or 48 weeks, or received PEGINTRON and REBETOL alone as a control.
During the ongoing review of the study by the Data Safety Monitoring Board
(DSMB), it was recommended that patients in the lower-dose boceprevir arms
who demonstrated a substantial antiviral response during treatment cross
over to boceprevir 800 mg TID in combination with PEGINTRON and REBETOL for
an additional 24 weeks. Patients who did not demonstrate a substantial
antiviral response during treatment were discontinued from the study. In
addition, patients in the control arm who did not respond to PEGINTRON and
REBETOL alone were allowed to cross over to boceprevir 800 mg TID in
combination with PEGINTRON and REBETOL. Patients received a maximum of 24
weeks of the optimized regimen (boceprevir 800 mg TID in combination with
PEGINTRON and REBETOL). In all, 357 patients were enrolled at centers in
the United States and Europe, including 348 patients who received
boceprevir at some point in the study.

In this study of well-documented null nonresponders, some patients
achieved a sustained virologic response (SVR). Overall, 7-14 percent of
patients in the boceprevir crossover arms achieved SVR compared to 2
percent in the control arm. SVR was associated with early virologic
response and a longer course of therapy (more than 36 weeks). While potent
antiviral activity with boceprevir was seen in the study, with viral loads
in some patients decreasing below the limit of detection, viral loads for
other patients decreased and then rebounded to baseline levels while on
therapy and some patients relapsed following the end of treatment. Several
resistant variants were observed in these patients. These HCV variants are
similar to those reported after treatment with other HCV protease
inhibitors and those previously observed in boceprevir in vitro studies.
Whether the results of this study would have been different had all
patients been started with the optimized regimen of boceprevir 800 mg TID
in combination with PEGINTRON and REBETOL -- and with treatment extending
to 48 weeks -- is not known.

"Although interferon nonresponders appear to respond to HCV protease
inhibition, it seems that some significant element of interferon response
is needed to achieve a sustained virologic response in the majority of
these patients," said Eugene R. Schiff, M.D., chief, division of hepatology
and director, Center for Liver Disease, University of Miami Miller School
of Medicine, and the lead investigator of the study.

Schering-Plough said that in patients with little to no interferon
response, alternative treatment strategies are required, and the company
will continue to explore regimens containing boceprevir, PEGINTRON and
REBETOL in the Phase II setting, using the insights gained in this initial
study.

About PEGINTRON

In the United States, PEGINTRON is indicated for use alone or with
ribavirin for the treatment of chronic hepatitis C in patients with
compensated liver disease who have not been previously treated with
interferon alpha and who are at least 18 years of age. PEGINTRON is
indicated for 48 weeks of treatment in the United States.

Important Safety Information Regarding U.S. Labeling for PEGINTRON and
REBETOL

Alpha interferons, including PEGINTRON and INTRON(R) A, may cause or
aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic,
and infectious disorders. Patients should be monitored closely with
periodic clinical and laboratory evaluations. Patients with persistently
severe or worsening signs or symptoms of these conditions should be
withdrawn from therapy. In many, but not all cases, these disorders resolve
after stopping PEGINTRON and/or INTRON A therapy.

Use with Ribavirin: Ribavirin may cause birth defects and/or death of
the unborn child. Extreme care must be taken to avoid pregnancy in female
patients and in female partners of male patients. Ribavirin causes
hemolytic anemia. The anemia associated with REBETOL therapy may result in
a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and
should be considered a potential carcinogen

Contraindications

PEGINTRON is contraindicated in patients with hypersensitivity to
PEGINTRON or any other component of the product, autoimmune hepatitis, and
hepatic decompensation (Child-Pugh score greater than 6 [class B and C]) in
cirrhotic CHC patients before or during treatment. INTRON A (Interferon
alfa- 2b, recombinant) for Injection is contraindicated in patients with
hypersensitivity to INTRON A or any component of the product, autoimmune
hepatitis, and decompensated liver disease. PEGINTRON or INTRON A in
combination with REBETOL therapy is additionally contraindicated in
patients with hypersensitivity to ribavirin or any other component of the
product, women who are pregnant, men whose female partners are pregnant,
patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell
anemia), and patients with creatinine clearance less than 50 mL/min.

Avoid Pregnancy

REBETOL therapy should not be started until a report of a negative
pregnancy test has been obtained immediately prior to planned initiation of
therapy. Extreme care must be taken to avoid pregnancy in female patients
and in female partners of male patients during therapy and 6 months post-
treatment. Patients should use at least two effective forms of
contraception and have monthly pregnancy tests during therapy and for 6
months after completion of therapy. A Ribavirin Pregnancy Registry has been
established to monitor maternal-fetal outcomes of pregnancies in female
patients and female partners of male patients exposed to ribavirin during
treatment, and for 6 months following cessation of treatment. Physicians
and patients are encouraged to report such cases by calling 1-800-593-2214.

Incidence of Adverse Events

There are no new adverse events specific to PEGINTRON as compared to
INTRON A; however, the incidence of some (e.g., injection site reactions,
fever, rigors, nausea) were higher. The most common adverse events
associated with PEGINTRON were "flu-like" symptoms, occurring in
approximately 50% of patients, which may decrease in severity as treatment
continues. Application site disorders were common (47%), but all were mild
(44%) or moderate (4%) and no patient discontinued, and included injection
site inflammation and reaction (i.e., bruise, itchiness, irritation).
Injection site pain was reported in 2% of patients receiving PEGINTRON.
Alopecia (thinning of the hair) is also often associated with alpha
interferons including PEGINTRON.

Psychiatric adverse events, which include insomnia, were common (57%)
with PEGINTRON but similar to INTRON A (58%). Depression was most common at
29%. Suicidal behavior including ideation, suicidal attempts, and completed
suicides occurred in 1% of patients during or shortly after completing
treatment with PEGINTRON.

The following serious or clinically significant adverse events have
been reported at a frequency less than 1% with PEGINTRON or interferon
alpha: Severe decreases in neutrophil or platelet counts, hypothyroidism,
hyperglycemia, hypotension, arrhythmia, ulcerative and hemorrhagic colitis,
development or exacerbation of autoimmune disorders including thyroiditis,
RA, systemic lupus erythematosus, psoriasis, pulmonary disorders (dyspnea,
pulmonary infiltrates, pneumonitis and pneumonia, some resulting in patient
deaths), urticaria, angioedema, bronchoconstriction, anaphylaxis, retinal
hemorrhages, and cotton wool spots.

In the PEGINTRON/REBETOL combination trial, the incidence of serious
adverse events was 17% in the PEGINTRON/REBETOL groups compared to 14% in
the INTRON A/ REBETOL group. The incidence of severe adverse events in the
PEGINTRON/REBETOL combination therapy trial was 23% in the INTRON A/REBETOL
group and 31-34% in the PEGINTRON/REBETOL groups. Dose reductions due to
adverse reactions occurred in 42% of patients receiving PEGINTRON (1.5
mcg/kg)/REBETOL and in 34% of those receiving INTRON A/REBETOL.

Additional Safety Information

Relapse of drug addiction/overdose has occurred in patients on
PEGINTRON therapy. Aggressive behavior sometimes directed towards others
has occurred in patients with and without a previous psychiatric disorder
during PEGINTRON and/or INTRON A treatment and follow-up. If patients
develop psychiatric problems, including clinical depression, it is
recommended that patients be carefully monitored during treatment and in
the 6-month follow-up period. If psychiatric symptoms persist or worsen, or
suicidal ideation or aggressive behavior towards others is identified, it
is recommended that treatment with PEGINTRON and/or INTRON A be
discontinued, and the patient be carefully followed with psychiatric
intervention, as appropriate. Cases of encephalopathy have been observed in
some patients, usually elderly, treated with higher doses of PEGINTRON
and/or INTRON A. Ischemic and hemorrhagic cerebrovascular events have been
observed in patients treated with interferon alpha therapies, including
PEGINTRON and INTRON A. Dental and periodontal disorders have been reported
in patients receiving PEGINTRON or INTRON A in combination with REBETOL
therapy.

About Schering-Plough

Schering-Plough is a global science-based health care company with
leading prescription, consumer and animal health products. Through internal
research and collaborations with partners, Schering-Plough discovers,
develops, manufactures and markets advanced drug therapies to meet
important medical needs. Schering-Plough's vision is to earn the trust of
the physicians, patients and customers served by its approximately 33,500
people around the world. The company is based in Kenilworth, N.J., and its
Web site is http://www.schering-plough.com.

SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press
release includes certain "forward-looking statements" within the meaning of
the Private Securities Litigation Reform Act of 1995, including statements
relating to the company's clinical development plans and the potential for
boceprevir. Forward-looking statements relate to expectations or forecasts
of future events. Schering-Plough does not assume the obligation to update
any forward-looking statement. Many factors could cause actual results to
differ materially from Schering-Plough's forward-looking statements,
including market forces, economic factors, product availability, patent and
other intellectual property protection, current and future branded, generic
or over-the-counter competition, the regulatory process, and any
developments following regulatory approval, among other uncertainties. For
further details and a discussion of risks and uncertainties that may impact
forward-looking statements, see Schering-Plough's Securities and Exchange
Commission filings, including Part II, Item 1A, "Risk Factors" in the
company's second quarter 2007 10-Q.

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